Infectious Disease of the Brain - The JC Virus

The JC Virus

The reason for this post is two fold: (1) to bring awareness and spread information about a little known disease and (2) people close to me were recently affected by this disease. The disease in question is Progressive Multifocal Leukoencephalopathy, or PML as it will be abbreviated hereafter.

PML is a rare viral disease characterized by damage to myelin in the brain. It is caused by the JC virus. Now before we get into the specifics of PML or the JC virus itself let’s review some basics of how a virus works. Check out this quick video produced by NPR on how a virus infects another cell.

The video talks about how the flu virus invades our bodies but the same principles apply for any virus. The crazy thing is our bodies are full of all kinds of viruses all the time. That means our immune system is constantly trying to stay one step ahead of the invaders.

The JC virus is actually present in almost all of us (90%) as we have all probably been exposed at some point in our lives. It is constantly trying to replicate itself but in a healthy individual our immune system can suppress the virus and it is not a major concern. People that have compromised immune systems (i.e. AIDS patients or people exposed to chemotherapy) are at a greater risk of the JC virus causing harmful side effects due to their immune system’s inability to fight the virus anymore.
Essentially, once the virus isn’t receiving resistance from the immune system it is free to travel throughout the body and cross the blood brain barrier, which gives it direct access to the central nervous system. The blood brain barrier is a thin layer of endothelial cells that separates the circulating blood from fluid in your brain. It allows essential nutrients such as glucose and other metabolic products entry into your brain but keeps potential toxins out. Other organs do not have this added level of security because it is pretty easy to replace cells in other areas of your body. Neurons, however, exit the cell cycle early on and do not easily replicate themselves so it is essential for your body to protect and sustain the ones you do have.
The brain consists of white matter and gray matter. Gray matter is cell bodies. White matter is axons (which extend off the cell bodies and connect to other cells in the brain). The axons appear white in the brain because of myelin, which is a lipid (fat) that insulates the axon and allows the electrical signal to travel down the axon faster. The JC virus attacks this white matter by killing the cells that are responsible for producing it. These cells are called oligodendrocytes in the central nervous system. In short, the virus takes away the brain’s ability to communicate messages efficiently and, eventually, not at all. If there is not an electrical signal triggering the release of chemicals from the ends of the axons, that vital signal is not being transmitted to other nearby cells. Without cells receiving normal input and nutrients, the cell itself will eventually die.
Unfortunately, viruses are extremely hard to treat. As we saw in the video earlier, viruses “hijack” a cell’s DNA (or RNA if it is an RNA virus) and use the cell’s own DNA synthesis machinery to reproduce itself. Antiviral medications are really the only hope of stopping something like the JC virus and PML. A new drug, Brincidofovir, is currently in clinical trials for fighting PML. Brindcidofovir gained some momentum and publicity for being effective against the Ebola virus when treating patients here in the U.S. It is a modified form of another drug called cidofovir. The drug is connected with a lipid (fat) that makes it very easy to get into the cells. Cells have a membrane made up of lipids to keep bad stuff out. By attaching a lipid group to this drug, Brincidofovir can enter the cell very easily and increases its intracellular concentration, which makes it more ideal for fighting viruses. In addition to that, Brincidofovir has great oral bioavailability. This means that when administered orally, the drug is relatively unchanged by the time it reaches the circulatory system (which will transport it to the brain). Brincidofovir has shown good efficacy in fighting viruses in the few clinical studies they have done with it and in mice with suppressed immune systems that were injected with a virus.
Regardless of promising drugs in development, the prognosis of PML is not good at all. 50% of patients die within months of diagnosis and those that survive have serious neurological issues. The brain really takes a hard, fast hit with this virus. Overall, I hope this post will help spread awareness for a rare infectious disease of the brain and help inform other families that have had to deal with this devastating illness about the science behind it.